INTEGRATED OPTICAL DETECTION AND TRAPPING OF MICRO AND NANO BIOPARTICLES

Medical and molecular diagnostics are based on the detection of biological particles. The dimensions of these particles are typically in the micro to nano scale. Often these particles are detected by relatively large conventional microscopes and devices, requiring a large and well-equipped laboratory. For this reason, this technology is usually expensive and complex. In many cases, a patient has to go to a hospital for an investigation, after which several days should be waited for the results and the diagnosis. Over the past decade, a lot of research has been performed on point-of-care lab-on-chip applications. These devices can generate almost instantaneous results and allow monitoring of the patient's health status at home. These applications mostly use electrical and optical detection methods. On-chip optical components have contributed to the miniaturization of microscopy technology to the chip scale. Large amounts of diagnostic devices can be utilized in parallel in a single chip and diagnosis can be performed remarkably faster. In addition, this parallelization and the simple integration with electronics results in a large cost reduction. This low cost and high speed for chip-level optical devices are likely to be the milestones of the development of point-of-care platforms in the near future. This thesis focuses on the detection of micro and nano particles by chip-based optical detection, for which two different techniques are used. Labeled microparticles and label-free nanoparticles were detected and identified by photonic chips. The applications of these techniques are discussed in this thesis. On the one hand, microparticles, such as peripheral blood mononuclear cells (PBMCs), were detected by focusing grating couplers (FGCs) in a SiN waveguide platform. On the other hand, label-free dielectric nanoparticles were captured, detected and identified using plasmonic nanopores.

SiN is a CMOS compliant material with a high refractive index of about 2. Because of its transparency in the visible spectrum, it is a very interesting material for biosensor applications such as fluorescent detection. An integrated SiN platform was therefore used in this thesis for the detection of microparticles.

Microscopes and their objective lenses are often used for different detection techniques. They allow to focus light into and collect light from a single focus point. A miniaturized version of such microscope objective lenses was designed in this thesis and studied in an integrated SiN platform. The structures designed for this purpose consist of FGCs fed by a SiN waveguide and focusing the light above the surface of the chip. Those devices were designed by a phase matching technique. The focal characteristics of those devices were analyzed using Finite-Difference Time Domain (FDTD) simulations and a series of experiments. In this way, light could be focused at the desired locations and experimental dimensions of the focus could be realized with dimensions of 300 nm at a wavelength of 638 nm.

In this manner, microparticles could be detected analogously to conventional microscopy. In the integrated platform, FGCs were used for the excitation and collection of the fluorescent signal. A FGC was used for the excitation of the fluorescence while three FGCs were used for the collection of the emitted signal. All couplers were designed to overlap their focus for an efficient excitation and collection. The structures and their efficiency were modeled by FDTD simulations. The whole platform was integrated into a microfluidic channel for optimal characterization. In the excitation profile measurements, a confinement size less than 750 nm was measured for the focus spot at an excitation wavelength of 638 nm. Then, fluorescently labeled polystyrene particles of 1 μm and 15 μm and PBMCs were injected into the channel and their fluorescent signal was excited and recorded by the FGCs. The fluorescent signals were measured via a microscope-camera arrangement. The collection efficiency of the FGCs was analyzed using different models. Experimental collection efficiency was defined as the ratio between the fluorescent signal detected by the camera and the total fluorescence emitted by the particle. Efficiencies up to 0.11% were experimentally realized for 1 μm particles, which is in good agreement with the FDTD simulations. In addition, it was shown that the maximum experimental fluorescence efficiency is inversely proportional to the dimensions of the particles. These results will contribute to chip-based  cytometry and spectroscopy applications.

For detection of nanoparticles, it is necessary to focus the light in regions below the diffraction limit. Plasmonic structures allow to focus light in these nanoscale dimensions. Nano apertures are often used to detect nanoparticles such as proteins using electrical and optical techniques. Plasmonic nanopores are metallic nano apertures that are realized by perforating a thin membrane connecting two electrolyte chambers. It was shown that nanopores with a specific geometry can identify different molecules by means of Surface Enhanced Raman Spectroscopy (SERS). For label-free detection of individual dielectric nanoparticles, it is necessary to confine the field in a dimension similar to the size of the particle. In addition, the Brownian motion of such particles limits the total amount of photons that can be detected. In this thesis, it is demonstrated that plasmonic nanopores can be used to capture and detect 20 nm polystyrene particles in solution by means of SERS. This opens interesting perspectives for the detection of small biological particles and nanotribological studies.